tbuckley/cabot-search huggingface dataset:
The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
Authors: Nilufer Rahmioglu, Sally Mortlock, Marzieh Ghiasi, Peter L. Møller, Lilja Stefansdottir, Geneviève Galarneau, Constance Turman, Rebecca Danning, Matthew H. Law, Yadav Sapkota, Paraskevi Christofidou, Sini Skarp, Ayush Giri, Karina Banasik, Michal Krassowski, Maarja Lepamets, Błażej Marciniak, Margit Nõukas, Danielle Perro, Eeva Sliz, Marta Sobalska-Kwapis, Gudmar Thorleifsson, Nura F. Topbas-Selcuki, Allison Vitonis, David Westergaard, Ragnheidur Arnadottir, Kristoffer S. Burgdorf, Archie Campbell, Cecilia S. K. Cheuk, Caterina Clementi, James Cook, Immaculata De Vivo, Amy DiVasta, O. Dorien, Jacqueline F. Donoghue, Todd Edwards, Pierre Fontanillas, Jenny N. Fung, Reynir T. Geirsson, Jane E. Girling, Paivi Harkki, Holly R. Harris, Martin Healey, Oskari Heikinheimo, Sarah Holdsworth-Carson, Isabel C. Hostettler, Henry Houlden, Sahar Houshdaran, Juan C. Irwin, Marjo-Riitta Jarvelin, Yoichiro Kamatani, Stephen H. Kennedy, Ewa Kepka, Johannes Kettunen, Michiaki Kubo, Bartosz Kulig, Venla Kurra, Hannele Laivuori, Marc R. Laufer, Cecilia M. Lindgren, Stuart MacGregor, Massimo Mangino, Nicholas G. Martin, Charoula Matalliotaki, Michail Matalliotakis, Alison D. Murray, Anne Ndungu, Camran Nezhat, Catherine M. Olsen, Jessica Opoku-Anane, Sandosh Padmanabhan, Manish Paranjpe, Maire Peters, Grzegorz Polak, David J. Porteous, Joseph Rabban, Kathyrn M. Rexrode, Hanna Romanowicz, Merli Saare, Liisu Saavalainen, Andrew J. Schork, Sushmita Sen, Amy L. Shafrir, Anna Siewierska-Górska, Marcin Słomka, Blair H. Smith, Beata Smolarz, Tomasz Szaflik, Krzysztof Szyłło, Atsushi Takahashi, Kathryn L. Terry, Carla Tomassetti, Susan A. Treloar, Arne Vanhie, Katy Vincent, Kim C. Vo, David J. Werring, Eleftheria Zeggini, Maria I. Zervou, Kari Stefansson, Mette Nyegaard, Paivi Harkki, Oskari Heikinheimo, Johannes Kettunen, Venla Kurra, Hannele Laivuori, Outi Uimari, Geneviève Galarneau, Caterina Clementi, Piraye Yurttas-Beim, Pierre Fontanillas, Joyce Y. Tung, Sosuke Adachi, Julie E. Buring, Paul M. Ridker, Thomas D’Hooghe, George N. Goulielmos, Dharani K. Hapangama, Caroline Hayward, Andrew W. Horne, Siew-Kee Low, Hannu Martikainen, Daniel I. Chasman, Peter A. W. Rogers, Philippa T. Saunders, Marina Sirota, Tim Spector, Dominik Strapagiel, Joyce Y. Tung, David C. Whiteman, Linda C. Giudice, Digna R. Velez-Edwards, Outi Uimari, Peter Kraft, Andres Salumets, Dale R. Nyholt, Reedik Mägi, Kari Stefansson, Christian M. Becker, Piraye Yurttas-Beim, Valgerdur Steinthorsdottir, Mette Nyegaard, Stacey A. Missmer, Grant W. Montgomery, Andrew P. Morris, Krina T. Zondervan
Journal: Nature Genetics (2023)
Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury
Authors: Ji Young Kim, Josie A. Silvaroli, Gabriela Vasquez Martinez, Bijay Bisunke, Alanys V. Luna Ramirez, Laura A. Jayne, Mei Ji He Ho Feng, Bhavya Girotra, Shirely M. Acosta Martinez, Corynne R. Vermillion, Isaac Z. Karel, Nicholas Ferrell, Noah Weisleder, Sangwoon Chung, John W. Christman, Craig R. Brooks, Sethu M. Madhavan, Kari R. Hoyt, Rachel E. Cianciolo, Anjali A. Satoskar, Diana Zepeda-Orozco, Jennifer C. Sullivan, Alan J. Davidson, Amandeep Bajwa, Navjot Singh Pabla
Journal: Kidney International (2023)
Doctors have a role in tackling air pollution: here’s how some are rising to the challenge
Authors: Sally Howard
Journal: BMJ (2023)

After Ella Adoo-Kissi-Debrah, the case for GPs and other medics to become clean air champions is growing, says <b>Sally Howard</b>. And some are responding—with solutions from individual activism to technological tools, and the UK's first environmental air pollution clinic for children
Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing
Authors: Runwei Yang, Xinran Feng, Alejandra Arias-Cavieres, Robin M. Mitchell, Ashleigh Polo, Kaining Hu, Rong Zhong, Cai Qi, Rachel S. Zhang, Nathaniel Westneat, Cristabel A. Portillo, Marcelo A. Nobrega, Christian Hansel, Alfredo J. Garcia III, Xiaochang Zhang
Journal: Neuron (2023)
Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter
Authors: Xiao-Na Zhu, Jie Li, Gao-Lin Qiu, Lin Wang, Chen Lu, Yi-Ge Guo, Ke-Xin Yang, Fang Cai, Tao Xu, Ti-Fei Yuan, Ji Hu
Journal: Neuron (2023)
Gasdermin-E mediates mitochondrial damage in axons and neurodegeneration
Authors: Dylan V. Neel, Himanish Basu, Georgia Gunner, Matthew D. Bergstresser, Richard M. Giadone, Haeji Chung, Rui Miao, Vicky Chou, Eliza Brody, Xin Jiang, Edward Lee, Michelle E. Watts, Christine Marques, Aaron Held, Brian Wainger, Clotilde Lagier-Tourenne, Yong-Jie Zhang, Leonard Petrucelli, Tracy L. Young-Pearse, Alice S. Chen-Plotkin, Lee L. Rubin, Judy Lieberman, Isaac M. Chiu
Journal: Neuron (2023)
Tumor PD-L1 engages myeloid PD-1 to suppress type I interferon to impair cytotoxic T lymphocyte recruitment
Authors: John D. Klement, Priscilla S. Redd, Chunwan Lu, Alyssa D. Merting, Dakota B. Poschel, Dafeng Yang, Natasha M. Savage, Gang Zhou, David H. Munn, Padraic G. Fallon, Kebin Liu
Journal: Cancer Cell (2023)

The cellular and molecular mechanisms underlying tumor cell PD-L1 (tPD-L1) function in tumor immune evasion are incompletely understood. We report here that tPD-L1 does not suppress cytotoxic T lymphocyte (CTL) activity in co-cultures of tumor cells and tumor-specific CTLs and exhibits no effect on primary tumor growth. However, deleting tPD-L1 decreases lung metastasis in a CTL-dependent manner in tumor-bearing mice. Depletion of myeloid cells or knocking out PD-1 in myeloid cells (mPD-1) impairs tPD-L1 promotion of tumor lung metastasis in mice. Single-cell RNA sequencing (scRNA-seq) reveals that tPD-L1 engages mPD-1 to activate SHP2 to antagonize the type I interferon (IFN-I) and STAT1 pathway to repress Cxcl9 and impair CTL recruitment to lung metastases. Human cancer patient response to PD-1 blockade immunotherapy correlates with IFN-I response in myeloid cells. Our findings determine that tPD-L1 engages mPD-1 to activate SHP2 to suppress the IFN-I-STAT1-CXCL9 pathway to impair CTL tumor recruitment in lung metastasis.
Cancer hallmarks intersect with neuroscience in the tumor microenvironment
Authors: Douglas Hanahan, Michelle Monje
Journal: Cancer Cell (2023)

The mechanisms underlying the multistep process of tumorigenesis can be distilled into a logical framework involving the acquisition of functional capabilities, the so-called hallmarks of cancer, which are collectively envisaged to be necessary for malignancy. These capabilities, embodied both in transformed cancer cells as well as in the heterotypic accessory cells that together constitute the tumor microenvironment (TME), are conveyed by certain abnormal characteristics of the cancerous phenotype. This perspective discusses the link between the nervous system and the induction of hallmark capabilities, revealing neurons and neuronal projections (axons) as hallmark-inducing constituents of the TME. We also discuss the autocrine and paracrine neuronal regulatory circuits aberrantly activated in cancer cells that may constitute a distinctive "enabling" characteristic contributing to the manifestation of hallmark functions and consequent cancer pathogenesis.
Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut
Authors: Jinzhi Duan, Juan D. Matute, Lukas W. Unger, Thomas Hanley, Alexandra Schnell, Xi Lin, Niklas Krupka, Paul Griebel, Conner Lambden, Brandon Sit, Joep Grootjans, Michal Pyzik, Felix Sommer, Sina Kaiser, Maren Falk-Paulsen, Helmut Grasberger, John Y. Kao, Tobias Fuhrer, Hai Li, Donggi Paik, Yunjin Lee, Samuel Refetoff, Jonathan N. Glickman, Adrienne W. Paton, Lynn Bry, James C. Paton, Uwe Sauer, Andrew J. Macpherson, Philip Rosenstiel, Vijay K. Kuchroo, Matthew K. Waldor, Jun R. Huh, Arthur Kaser, Richard S. Blumberg
Journal: Immunity (2023)
Networks of care to strengthen primary healthcare in resource constrained settings
Authors: Enoch Oti Agyekum, Katherine Kalaris, Blerta Maliqi, Allisyn C Moran, Andrews Ayim, Sanam Roder-DeWan
Journal: BMJ (2023)

Quality of Care Key messages• Collaboration between healthcare facilities, in the form of networks of care has the potential to improve efficiency, quality, and outcomes in resource constrained settings• Case studies of successful networks of care signal that the approach can strengthen structural and, most importantly, relational elements among facilities• Networks of care are being imple- mented at primary healthcare level in many countries, providing opportunities for further research on its effects on 21 July
Regular measurement is essential but insufficient to improve quality of healthcare
Authors: Ambrose Agweyu, Kathleen Hill, Theresa Diaz, Debra Jackson, Binyam G Hailu, Moise Muzigaba
Journal: BMJ (2023)

<b>Ambrose Agweyu and colleagues</b> argue that large scale improvements in quality of healthcare require strong change management as well as health information systems that can provide continuous and rapid feedback
Decolonisation and quality of care
Authors: Bernice Yanful, Meghan Bruce Kumar, Ezequiel García-Elorrio, Chris Atim, Sanam Roder-DeWan
Journal: BMJ (2023)

Delivering high quality healthcare for all requires recognising the legacies of colonialism in driving power asymmetries and producing inequitable health outcomes both within and between countries say <b>Bernice Yanful and colleagues</b>
Service delivery redesign is a process, not a model of care
Authors: Sanam Roder-DeWan, Supriya Madhavan, Savitha Subramanian, Kojo Nimako, Talib Lashari, Amith Nagaraj Bathula, Ramkumar Sathurappan, Sampath Kumar, Mickey Chopra
Journal: BMJ (2023)

Quality of CareService delivery redesign is a process, not a model of care Sanam Roder-DeWan and colleagues call for wider application of the principles of service delivery redesign to provide accessible, high quality services across healthcare Key messages• Service delivery redesign has become synonymous with one model of care for one condition.• Service delivery redesign is a process that allows development of innovative solutions that are tailored to specific needs• Government support and commu- nity input from the start help ensure improvement in quality of care on 21 July
Identifying vulnerable populations in the electronic Framingham Heart Study to improve digital device adherence
Authors: Mirja Mittermaier, Kaushik P. Venkatesh, Joseph C. Kvedar
Journal: npj Digital Medicine (2023)

The usage of digital devices in clinical and research settings has rapidly increased. Despite their promise, optimal use of these devices is often hampered by low adherence. The relevant factors predictive of long-term adherence have yet to be fully explored. A recent study investigated device usage over 12 months in a cohort of the electronic Framingham Heart Study. It identified sociodemographic and health-related factors associated with the long-term use of three digital health components: a smartphone app, a digital blood pressure cuff, and a smartwatch. The authors found that depressive symptoms and lower self-rated health were associated with lower smartwatch usage. Female sex and higher education levels were associated with higher app-based survey completion. Here, we discuss factors predictive for adherence and personalized strategies to promote adherence to digital tools.
COVID-19–associated mucormycosis: a systematic review and meta-analysis of 958 cases
Authors: Laşin Özbek, Umur Topçu, Mehtap Manay, Buğra Han Esen, Sevval Nur Bektas, Serhat Aydın, Barış Özdemir, Sofya N. Khostelidi, Nikolai Klimko, Oliver Cornely, Johnny Zakhour, Souha S. Kanj, Danila Seidel, Martin Hoenigl, Önder Ergönül
Journal: Clinical Microbiology and Infection (2023)
Exploring the genetic landscape of HCV-related B-cell lymphomas using whole exome sequencing
Authors: Marine Armand, Michaël Degaud, Bruno Tesson, Cécile Laurent, Manon Vavasseur, Mélanie Parisot, Bénédicte Hoareau-Coudert, Danielle Canioni, Jean Marie Michot, Frédéric Charlotte, Véronique Meignin, Camille Laurent, Alexandra Traverse-Gléhen, Diane Damotte, Emmanuel Bachy, Caroline Besson, Olivier Hermine, Frédéric Davi, Lucile Couronné
Journal: Leukemia (2023)
Prevalence of human immunodeficiency virus, syphilis, and hepatitis B and C virus infections in pregnant women: a systematic review and meta-analysis
Authors: Shouyuan Wu, Jianjian Wang, Qiangqiang Guo, Hui Lan, Yajia Sun, Mengjuan Ren, Yunlan Liu, Ping Wang, Ling Wang, Renfeng Su, Juanjuan Zhang, Yaolong Chen, Guobao Li
Journal: Clinical Microbiology and Infection (2023)

BackgroundAt the 74th World Health Assembly, the WHO issued a strategy for the prevention and control of several major infectious diseases. To achieve the WHO-initiated targets for these infectious diseases, the elimination of mother-to-child transmission is essential. To date, a systematic review of the global and regional prevalence of infections with relevant mother-to-child transmission and outside the spectrum of congenital infections is lacking.ObjectivesWe aimed to systematically review the prevalence of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis in pregnant women.Data sourcesMEDLINE, Embase, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang database and China Biology Medicine disc database, and five WHO Regional Index Medicus databases.Study eligibility criteriaOriginal studies reporting the prevalence of infection or coinfection of HIV, HBV, HCV, and syphilis in pregnant women.MethodsThis systematic review followed the preferred reporting items for systematic reviews and meta-analyses 2020 checklist. We used random-effects models to generate pooled prevalence estimates for each infection.ResultsThe global pooled prevalence in pregnant women of HIV, HBV, HCV, and syphilis was 2.9% (95% CI, 2.4–3.4%), 4.8% (3.8–5.8%), 1.0% (0.8–1.3%), and 0.8% (0.7–0.9%). The pooled prevalence of HIV, HBV, HCV, and syphilis in low-income countries was higher than the global level (HIV: 5.2% [1.6–10.5%); HBV: 6.6% (5.4–7.9%); HCV: 2.7% (1.6–4.1%); syphilis: 3.3% (2.2–4.6%]). The pooled prevalence of HIV, HBV, HCV, and syphilis in lower-middle-income countries was higher than the global level (HIV: 2.9% [0.8–6.1%]; HBV: 4.9% [3.8–6.1%]; HCV: 2.3% [1.2–3.6%]; syphilis: 1.5% [1.0–2.2%]).ConclusionsThe prevalence of these infections among pregnant women was particularly high in resource-poor settings. The relevance and feasibility of current global practice guidelines for the prevention of mother-to-child transmission of these infections in lower-middle-income countries must be evaluated, including timely access to screening and therapeutics.
The Stiffness‐Sensitive Transcriptome of Human Tendon Stromal Cells (Adv. Healthcare Mater. 7/2023)
Authors: Amro A. Hussien, Barbara Niederoest, Maja Bollhalder, Nils Goedecke, Jess G. Snedeker
Journal: Advanced Healthcare Materials (2023)

Matrix Stiffness Extracellular matrix stiffness-sensing studies are typically carried out using cells that have acquired “mechanical memory” through progressive passaging in rigid mechanical environments, e.g., tissue culture plastic (TCP). This confounds the mechanistic experiments that investigate matrix stiffness-driven mechanosensing programs. In article 2101216, Jess G. Snedeker and co-workers report the formulation of a mechano-variant silicone-based platform with tunable elasticity and tendon-like elastic moduli, and with optimized chemistry to make it amenable to large-scale cell expansion practices.
Spatiotemporal Regulation of Injectable Heterogeneous Silk Gel Scaffolds for Accelerating Guided Vertebral Repair (Adv. Healthcare Mater. 7/2023)
Authors: Tianji Wang, Keyin Liu, Jing Wang, Geng Xiang, Xiaofan Hu, Hao Bai, Wei Lei, Tiger H. Tao, Yafei Feng
Journal: Advanced Healthcare Materials (2023)

Silk Hydrogels Article 2202210 by Wei Lei, Tiger H. Tao, Yafei Feng, and co-workers reports heterogeneous silk hydrogel loaded with sEVs and DFO/YC-1, which is used to provide vertebral body filling support, spatiotemporally regulate local microenvironment, and achieve bone repair and regeneration. This study provides structural and functional strategies for the clinical applications of vertebral augmentation.
Flexible Skin Patch Enabled Tumor Hybrid Thermophysical Therapy and Adaptive Antitumor Immune Response (Adv. Healthcare Mater. 7/2023)
Authors: Xuyang Sun, Tao Wu, Minghui Duan, Bo Yuan, Xiyu Zhu, Hongzhang Wang, Jing Liu
Journal: Advanced Healthcare Materials (2023)

Flexible Skin Patches In article 2202872 by Xuyang Sun, Hongzhang Wang, Jing Liu and co-workers, a flexible skin patch with improved adhesiveness to skin is designed for conformable and non-invasive tumor therapy. This multifunctional technology can achieve severe destruction on tumor via an “ice and fire” mechanism, mediated by cryoablation, magnetic hyperthermia, as well as immune response activation.
Metabolic reprogramming via an engineered PGC-1α improves human chimeric antigen receptor T-cell therapy against solid tumors
Authors: Konstantinos Lontos, Yiyang Wang, Supriya K Joshi, Andrew T Frisch, McLane J Watson, Alok Kumar, Ashley V Menk, Yupeng Wang, Rachel Cumberland, Jason Lohmueller, Esteban Carrizosa, Benjamin Boyerinas, Greg M Delgoffe
Journal: Journal for ImmunoTherapy of Cancer (2023)

Cellular immunotherapies for cancer represent a means by which a patient's immune system can be augmented with high numbers of tumor-specific T cells. Chimeric antigen receptor (CAR) therapy involves genetic engineering to 'redirect' peripheral T cells to tumor targets, showing remarkable potency in blood cancers. However, due to several resistance mechanisms, CAR-T cell therapies remain ineffective in solid tumors. We and others have shown the tumor microenvironment harbors a distinct metabolic landscape that produces a barrier to immune cell function. Further, altered differentiation of T cells within tumors induces defects in mitochondrial biogenesis, resulting in severe cell-intrinsic metabolic deficiencies. While we and others have shown murine T cell receptor (TCR)-transgenic cells can be improved through enhanced mitochondrial biogenesis, we sought to determine whether human CAR-T cells could be enabled through a metabolic reprogramming approach.
LAL deficiency induced myeloid-derived suppressor cells as targets and biomarkers for lung cancer
Authors: Ting Zhao, Sheng Liu, Nasser H Hanna, Shadia Jalal, Xinchun Ding, Jun Wan, Cong Yan, Hong Du
Journal: Journal for ImmunoTherapy of Cancer (2023)

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells in tumor microenvironment, which suppress antitumor immunity. Expansion of various MDSC subpopulations is closely associated with poor clinical outcomes in cancer. Lysosomal acid lipase (LAL) is a key enzyme in the metabolic pathway of neutral lipids, whose deficiency (LAL-D) in mice induces the differentiation of myeloid lineage cells into MDSCs. These Lal-/- MDSCs not only suppress immune surveillance but also stimulate cancer cell proliferation and invasion. Understanding and elucidating the underlying mechanisms of MDSCs biogenesis will help to facilitate diagnosis/prognosis of cancer occurrence and prevent cancer growth and spreading.Single-cell RNA sequencing (scRNA-seq) was performed to distinguish intrinsic molecular and cellular differences between normal versus Lal-/- bone marrow-derived Ly6G+ myeloid populations in mice. In humans, LAL expression and metabolic pathways in various myeloid subsets of blood samples of patients with non-small cell lung cancer (NSCLC) were assessed by flow cytometry. The profiles of myeloid subsets were compared in patients with NSCLC before and after the treatment of programmed death-1 (PD-1) immunotherapy.scRNA-seq of Lal-/- CD11b+Ly6G+ MDSCs identified two distinctive clusters with differential gene expression patterns and revealed a major metabolic shift towards glucose utilization and reactive oxygen species (ROS) overproduction. Blocking pyruvate dehydrogenase (PDH) in glycolysis reversed Lal-/- MDSCs' capabilities of immunosuppression and tumor growth stimulation and reduced ROS overproduction. In the blood samples of human patients with NSCLC, LAL expression was significantly decreased in CD13+/CD14+/CD15+/CD33+ myeloid cell subsets. Further analysis in the blood of patients with NSCLC revealed an expansion of CD13+/CD14+/CD15+ myeloid cell subsets, accompanied by upregulation of glucose-related and glutamine-related metabolic enzymes. Pharmacological inhibition of the LAL activity in the blood cells of healthy participants increased the numbers of CD13+ and CD14+ myeloid cell subsets. PD-1 checkpoint inhibitor treatment in patients with NSCLC reversed the increased number of CD13+ and CD14+ myeloid cell subsets and PDH levels in CD13+ myeloid cells.These results demonstrate that LAL and the associated expansion of MDSCs could serve as targets and biomarkers for anticancer immunotherapy in humans.
Invasive margin tissue-resident macrophages of high CD163 expression impede responses to T cell-based immunotherapy
Authors: Marit J van Elsas, Camilla Labrie, Anders Etzerodt, Pornpimol Charoentong, Jordi J C van Stigt Thans, Thorbald Van Hall, Sjoerd H van der Burg
Journal: Journal for ImmunoTherapy of Cancer (2023)

Primary and secondary resistance is a major hurdle in cancer immunotherapy. Therefore, a better understanding of the underlying mechanisms involved in immunotherapy resistance is of pivotal importance to improve therapy outcome.Here, two mouse models with resistance against therapeutic vaccine-induced tumor regression were studied. Exploration of the tumor microenvironment by high dimensional flow cytometry in combination with therapeutic in vivo settings allowed for the identification of immunological factors driving immunotherapy resistance.Comparison of the tumor immune infiltrate during early and late regression revealed a change from tumor-rejecting toward tumor-promoting macrophages. In concert, a rapid exhaustion of tumor-infiltrating T cells was observed. Perturbation studies identified a small but discernible CD163hi macrophage population, with high expression of several tumor-promoting macrophage markers and a functional anti-inflammatory transcriptome profile, but not other macrophages, to be responsible. In-depth analyses revealed that they localize at the tumor invasive margins and are more resistant to Csf1r inhibition when compared with other macrophages. In vivo studies validated the activity of heme oxygenase-1 as an underlying mechanism of immunotherapy resistance. The transcriptomic profile of CD163hi macrophages is highly similar to a human monocyte/macrophage population, indicating that they represent a target to improve immunotherapy efficacy.In this study, a small population of CD163hi tissue-resident macrophages is identified to be responsible for primary and secondary resistance against T-cell-based immunotherapies. While these CD163hi M2 macrophages are resistant to Csf1r-targeted therapies, in-depth characterization and identification of the underlying mechanisms driving immunotherapy resistance allows the specific targeting of this subset of macrophages, thereby creating new opportunities for therapeutic intervention with the aim to overcome immunotherapy resistance.